tbuckley/cabot-search huggingface dataset:
Clinical characteristics and outcomes of SARS-CoV-2 infection in patients with genitourinary cancer.
Authors: Dorothy Kenny, Jue Wang
Journal: Journal of Clinical Oncology (2023)

7 Background: Cancer patients have increased risk for severe outcomes related to SARS-CoV-2 infection (COVID-19), due to their increased vulnerability to infection, older age, and comorbidities in comparison to the general population. While multiple studies have been completed examining outcomes of COVID-19 infection in cancer patients overall, there has been limited investigation into the outcomes of COVID-19 infection in patients with genitourinary (GU) cancers. Methods: We completed a single institution retrospective study to examine the outcomes of adults with GU cancers and COVID-19 infection from March 10, 2020 to June 15, 2022. Baseline data included age, sex, BMI, type of malignancy, cancer status (stable or progressive disease, in remission), current and previous anticancer therapy received, and comorbidities. Results: Eighty-four patients with a GU cancer diagnosis and laboratory-confirmed SARS-CoV-2 infection were identified. Seventy-nine (94%) were male and the median age was 64 years (range 24-91). Forty-four (52%) were non-Hispanic white, 28 (33%) were Hispanic, and 11 (13%) were African-American. Prostate cancer was the most common (n = 45), followed by renal cell carcinoma (n = 20), testicular (n = 9), bladder (n = 6), and penile cancer (n = 3). Eight patients had ≥2 episodes of COVID-19 infection. Sixty-three percent of patients were unvaccinated at the time of infection, while 37% of patients had breakthrough infection. Hospitalization was required for 39.3% (n = 33), with 4.8% (n = 4) requiring ICU admission. Of the patients requiring hospitalization, 26.2% (n = 22) died. Hospitalization was associated with having ≥2 comorbidities (OR 18.6 [95% CI, 3.1-111.8], p&lt;0.01) and receiving active cancer treatment (OR 12.4 [95% CI, 1.92-79.7], p&lt; 0.01). Mortality was associated with advanced age (OR 21.7 [95% CI, 1.40-341.7], p=0.03) and ≥2 comorbidities (OR 19.2 [95% CI, 3.02-122.5], p=0.02). Vaccination was negatively associated with both hospitalization (OR 0.04 [95% CI, 0.02-0.91], p=0.04) and mortality (OR 0.14 [95% CI, 0.02-0.84], p=0.03). Conclusions: Among patients with GU cancer, advanced age and comorbidities are associated with adverse outcomes of COVID-19 infection; vaccination is protective. With the emergence of variants and waning immunity of vaccines, our findings highlight the importance of development and implementation of enhanced mitigation strategies in cancer patients, especially those undergoing active cancer treatment.
Outcomes of first subsequent taxane (FST) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who previously received docetaxel intensification (DI) for metastatic castration-sensitive prostate cancer (mCSPC).
Authors: Gabrielle Robin, Naveen S. Basappa, Scott A. North, Sunita Ghosh, Michael Paul Kolinsky
Journal: Journal of Clinical Oncology (2023)

72 Background: The management of advanced prostate cancer continues to rapidly evolve, particularly with earlier use of survival prolonging therapies in mCSPC. Though approved prior to the use of intensification therapy in mCSPC, taxane-based chemotherapies remain a relevant option for pts with mCRPC. However, there is little evidence determining outcomes of taxane chemotherapies as FST in mCRPC pts who received DI in mCSPC. The purpose of this study is to compare outcomes between the survival prolonging taxanes, docetaxel (D) and cabazitaxel (C), as FST after DI. Methods: New patient consults seen at the Cross Cancer Institute from 1 July 2014 to 31 Dec 2020 were reviewed. Pts were considered eligible if they received DI for mCSPC and then received either D or C in mCRPC. Variables of interest were collected from the electronic medical record. The primary endpoint was ≥50% PSA response at 12 weeks relative to baseline for FST. Secondary endpoints included OS from mCSPC diagnosis, as well as PFS and OS from FST start date. PSA responses were compared using chi-squared test and time-based endpoints were compared using the Kaplan-Meier method. Results: 34 pts were identified: D = 22, C = 12 as FST. 91.2% of pts (D 95.5% vs C 83.3%) received FST in 2 nd line mCRPC. Median age at diagnosis (63.1 vs 67.1 yrs, p = 0.236) and median time to CRPC (18.6 vs 14.2 mos, p = 0.079) were similar for D and C, respectively. Median time to FST (24.1 vs 34.6 mos, p = 0.036) and OS from mCSPC diagnosis (30.9 vs 52.7 mos, p = 0.002) were significantly shorter for pts receiving C vs D. PSA responses occurred in 40.9% of pts treated with D compared to 25.0% treated with C (p = 0.645). There was no significant difference in median PFS (2.7 vs 3.5 mos, p = 0.727) or median OS (11.4 vs 8.1 mos, p = 0.132) from time of FST for pts treated with D vs C, respectively. Conclusions: Both D and C demonstrated activity as FST after DI in mCSPC. Pts who received C had shorter time to FST and OS from mCSPC. The reasons for this may reflect clinician preference for C in pts with aggressive or rapidly progressing disease. No difference was found in PSA response, PFS, or OS from FST with D compared to C. While limited by its retrospective nature and small sample size, this study suggests that D is active as FST despite treatment with DI in mCSPC.
Occurrence and prognostic significance of different histology relative to urinary tract tumors: A SEER population-based study.
Authors: Haoyang Liu, Junru Chen, Zhenhua Liu, Pengfei Shen, Hao Zeng
Journal: Journal of Clinical Oncology (2023)

485 Background: To evaluate the prevalence and prognostic value of variant histology in urinary tract tumors according to primary location and metastatic status. Methods: Using the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2015) databases, patients with urinary tract tumors were identified. Propensity Score Matching was used to balance the clinicopathologic features between different histologies. Kaplan-Meier plots were used to compare the cancer specific survival (CSS) and overall survival (OS) of different histologies. The cox regression analysis were also applied. Results: Of all 93,200 eligible patients with urinary tract tumors, 87,323 (93.7%) harbored bladder cancer (3,685 in M1 stage). Among them, urothelial tumors (UC) accounted for 96.67%, followed by squamous neoplasm (SCC), urachal carcinoma (Urachal), adenocarcinoma (Adeno), neuroendocrine tumors (NE) and tumor of Müllerian type (Müllerian). A total of 5877 (6.35%) harbored upper urinary tract tumors (950 in M1 stage). Among them, UC accounted for 96.39%, followed by SCC, Urachal, Müllerian, NE, Adeno. In patients with localized diseases, those with non-urothelial tumors had significantly worse prognosis in overall urinary tract tumors based on OS and CSS (P&lt;0.001). In terms of specific histology in bladder cancer (BC), patients with UC had most favorable prognosis, followed by Adeno, Urachal and Müllerian, while those with SCC and NE were associated with the worst survival outcomes. In patients with upper urinary tract tumors (UUTT), those with Müllerian had the best survival outcomes, followed by UC, while those with NE, Adeno, SCC, and Urachal had relatively worse prognosis. In M1 stage, although there was a statistical difference in OS and CSS between all patients with urothelial and non-urothelial tumors (P&lt;0.001), the 5-year survival rate (3.74%, 2.50%) and 5-year CSM (4.93%, 3.28%) were similar. In metastatic BC, there was no difference in OS among all histology. However, in terms of CSS, significant differences were still observed in patients with different histologies. In metastatic UUTT, no difference in survival was found among different histologies. After PSM, the similar results were observed in BC, while there is no statistical difference of survival among different histologies in UUTT, no matter the M stage. Cox analyses revealed that primary location, histology type, surgery, chemotherapy and M stage were the common and strong independent prognostic factors in both BC and UUTT. Conclusions: In urinary tract tumors, the incidence of different histology types between BC and UUTT is roughly similar. Overall, patient with variant histology have a worse prognosis than those with urothelial carcinoma. However, differences in survival among the histology types vary by primary location and metastatic status, especially the metastatic status.
Nivolumab plus cabozantinib vs sunitinib for first-line treatment of advanced renal cell carcinoma (aRCC): 3-year follow-up from the phase 3 CheckMate 9ER trial.
Authors: Mauricio Burotto, Thomas Powles, Bernard Escudier, Andrea B. Apolo, Maria Teresa Bourlon, Amishi Yogesh Shah, Cristina Suárez, Camillo Porta, Carlos H. Barrios, Martin Richardet, Howard Gurney, Elizabeth R Kessler, Yoshihiko Tomita, Jens Bedke, Saby George, Christian Scheffold, Peter Wang, Viktor Fedorov, Robert J. Motzer, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2023)

603 Background: First-line nivolumab plus cabozantinib (N+C) demonstrated superiority over sunitinib (S) with 25.4 mo minimum follow-up (median, 32.9 mo) in patients (pts) with aRCC in the CheckMate 9ER trial. Here, we report survival, response per blinded independent central review (BICR), and safety after 3 y minimum follow-up in all randomized pts and by IMDC risk score. Methods: Pts were randomized 1:1 (stratified by IMDC risk score, tumor PD-L1 expression, region) to N 240 mg flat dose IV Q2W + C 40 mg PO QD vs SUN 50 mg PO for 4 wk (6-wk cycles) until disease progression or unacceptable toxicity (max N treatment, 2 y). Primary endpoint: progression-free survival (PFS) by BICR. Secondary endpoints: overall survival (OS), objective response rate (ORR) by BICR, and safety. Results: In total, 323 pts were randomized to N+C and 328 to S. With 36.5 mo minimum follow-up (median, 44.0 mo), PFS and OS benefits were maintained with N+C vs S in intent-to-treat pts. Median PFS was 16.6 vs 8.4 mo (HR 0.59 [95% CI 0.49–0.71], P &lt; 0.0001) and median OS was 49.5 vs 35.5 mo (HR 0.70 [95% CI 0.56–0.87], P = 0.0014). ORR (95% CI) was higher with N+C vs S (56% [50–62] vs 28% [23–33]), and 13% vs 5% of pts achieved complete response (CR), respectively. Median duration of response was 22.1 vs 16.1 mo for N+C vs S. PFS, OS, and response are reported across prespecified IMDC risk groups in the table. Any-grade treatment-related adverse events (TRAEs) occurred in 97% vs 93% of pts treated with N+C vs S (grade ≥ 3 TRAE, 67% vs 55%). TRAEs led to discontinuation of C only in 10% of pts, N only in 10% of pts, N+C in 7% of pts, N or C in 28% of pts, and S in 11% of pts. Conclusions: After 3 y minimum follow-up, survival and response benefits were maintained with N+C and remained consistent with previous follow-ups. Median OS with N+C improved by 11.8 mo since the previous data cut. Responses with N+C were durable, with higher CR rates with N+C vs S regardless of IMDC risk group. No new safety signals emerged with additional follow-up in either arm. These results continue to support N+C as a first-line treatment for pts with aRCC. Clinical trial information: NCT03141177 . [Table: see text]
The impact of homologous recombination repair (HRR) gene mutation status on treatment (tx) patterns and clinical outcomes among patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) in the United States (US).
Authors: Pedro C. Barata, Ella X. Du, Hongbo Yang, Chunyi Xu, Helen Guo, Caroline Cui, Jonathan Nazari, Alexander Niyazov
Journal: Journal of Clinical Oncology (2023)

97 Background: There is a paucity of evidence that evaluates the impact of HRR mutation status on clinical outcomes in pts with mCRPC. This study assessed the real-world (rw) progression-free survival (rwPFS) based on HRR mutation status (HRR mutated [HRRm]), HRR wild type (HRRwt) among pts with mCRPC in the US. Methods: Data from pts with mCRPC initiating first line (1L) tx between 2016 and 2019 and known HRR status based on germline or tumor testing were retrospectively abstracted from medical charts by physicians in the US from 2021–2022. Pt demographic and clinical characteristics were summarized descriptively across subgroups by HRR status (HRRm vs HRRwt). HRRm was defined as a mutation in at least 1 of 12 genes of interest ( BRCA1, BRCA2, PALB2, ATM, ATR, CHEK2, FANCA, MLH1, MRE11A, NBN, RAD51C, CDK12), regardless of test type. RwPFS on 1L mCRPC tx was compared among pts with HRRm vs HRRwt genes and BRCA1/2 HRRm vs HRRwt genes using the Kaplan–Meier method and log-rank test. Results: A total of 80 physicians contributed data from charts of 130 pts (N=51 HRRm and N=79 HRRwt). Among pts with HRRm genes, 34 (67%) were positive for BRCA1 or BRCA2 mutations. In pts with known timing of testing (n=88), 33% were tested prior to initiation of 1L therapy and 67% after initiation of 1L therapy. In the 1L setting, novel hormonal therapy (NHT) was utilized in 29% of pts with HRRm vs 58% with HRRwt genes (P&lt;0.01). Chemotherapy was utilized in 43% of pts with HRRm vs 34% with HRRwt genes (P=0.40); docetaxel was the most common agent, utilized in 26% vs 27% of pts with HRRm vs HRRwt genes. Median rwPFS on 1L tx was 19 months (95% CI: 11–NE) vs 31 months (95% CI: 23–NE), P=0.11, for pts with HRRm vs HRRwt genes, respectively. RwPFS for pts with BRCA1/2 HRRm genes (N=34) vs HRRwt genes was 19 months (95% CI: 11–NE) vs 31 months (95% CI: 23–NE), P=0.17. Conclusions: In this rw study, genomic testing was performed frequently in later stages of metastatic disease. Pts with HRRm genes had numerically shorter rwPFS on 1L standard therapies compared with HRRwt pts. While unmet needs exist to optimize mCRPC txs and prolong disease progression irrespective of HRRm mutation status, further studies are warranted to further elucidate the prognostic role of HRRm and BRCA1/2 mutations on clinical outcomes.
Penile cancer: 20 years of experience in a reference oncology center in Mexico.
Authors: Yuridia Evangelina Rodriguez Rosales, Abraham Guerra Cepeda, Rubi Janday Najera, Francisco Daniel Rivera Valdés, David Hernandez Barajas, Oscar Vidal-Gutiérrez, Omar Alejandro Zayas-Villanueva
Journal: Journal of Clinical Oncology (2023)

6 Background: Penile cancer is a rare neoplasm (&lt;1%), being more common in underdeveloped countries, 10-20% of male neoplasms, with a mean age at diagnosis of 60 years. The number of annual cases in Mexico is only 660 cases, 0.35% of all neoplasms. Its initial symptomatology as a palpable or ulcerated lesion must be differentiated from infectious processes. From 30 to 60% of cases debut with inguinal lymphadenopathies and distant metastases in 1 to 10%. Methods: Cross-sectional, retrospective cohort study of patients diagnosed with penile cancer, who received medical care at the medical oncology service of the University Cancer Center from January 1, 1999 to December 31, 2019. Results: Of the 103 patients analyzed in this study, the mean age was 55 years (27-91 years), the highest level of schooling obtained was primary in 18.5%, being mostly from the state of Nuevo León in 61.1%. of the cases. The duration of symptoms was 17 months on average, and the time interval between diagnosis and receiving medical or surgical treatment was 97 days. Regarding the pathological characteristics of penile cancer, the average tumor size was 41.4mm, the most frequent histological type was squamous in 91.3%. Regarding the classification by clinical stages, patients in clinical stage I was 8%, II 10.6%, III 26.2% and IV 32%, not being recorded accurately in 23.3% of cases. The initial medical treatment was surgical in 81.5% of the cases, with partial phallectomy being the procedure of choice in 57.2% of the patients, with the presence of positive margins in 9.5% of the patients. Lymph node involvement was 71.2% of the cases and lymph node dissection was only performed in 31% of the patients. Those who received chemotherapy were 27.1% of the patients, the majority, 57.1% in the adjuvant setting, the most commonly used scheme was cisplatin with 5-fluoroacyl in 60.7%. Radiotherapy was used in 25.2% of the patients, being the adjuvant modality in 65.4% and in the palliative context in 34.6%, with an average dose of 46.5 Gy and 8 fractions. Conclusions: A diagnosis at an earlier age was observed in our court, being 55 years old vs 60 years old reported in the literature. A delay in diagnosis of up to 12 months has been reported in 15-50% in the literature, being higher in our population with a mean of 17.7 months. Poor adherence to treatment and clinical follow-up was observed, since one in 4 patients only goes to oncology once and loses follow-up. Penile cancer is a rare, psychologically devastating neoplasm with delayed diagnosis, advanced clinical disease, decreased survival, and high recurrence rates despite bimodal or trimodal treatment. A multidisciplinary team approach should be sought to achieve better oncological results and timely detection of cancer in earlier stages.
Differences in the tumor transcriptomic profile of patients (pts) with advanced prostate cancer (PCa) with and without diabetes mellitus (DM).
Authors: Nishita Tripathi, Haoran Li, Beverly Chigarira, Shruti Adidam Kumar, Kim JongTaek, Nicolas Sayegh, Georges Gebrael, Yeonjung Jo, Kamal Kant Kant Sahu, Vinay Mathew Thomas, Roberto Nussenzveig, Divyam Goel, Clara Tandar, Nityam Rathi, Umang Swami, Neeraj Agarwal, Benjamin L. Maughan
Journal: Journal of Clinical Oncology (2023)

244 Background: Pre-existing DM is associated with increased PCa specific and all-cause mortality in men with prostate cancer (PMID: 27652121). However, the underlying reasons are unclear. We hypothesized that transcriptomic profile of metastatic PCa pts with diagnosis of DM prior to the diagnosis of metastatic disease and start of systemic therapy will be different from those without DM. Methods: In this IRB-approved retrospective study, advanced PCa pts with available RNA profiling of treatment naïve tumor tissue through a CLIA-certified laboratory were included. Based on pre-existing DM prior to onset of metastatic disease, pts was grouped into DM and non-DM. Differential gene expression analysis between the two groups was performed using DeSeq2. These results were subjected to Gene Set Enrichment software analysis (GSEA) to identify pathways enriched in each cohort. Gene ontology analysis using TopGO software was done to identify the biological process occurring at the molecular level of these differentially expressed genes. All bioinformatic analysis was conducted in R studio, version 4.1.1. Results: 75 pts were eligible and included: 20 DM vs 55 non-DM. Baseline characteristics (DM vs non-DM): median age 63.5 vs 64 years; median PSA at diagnosis 20 vs 18.85ng/mL; de novo disease: 55% vs 43.6%; Gleason score ≥8: 60% vs 74.5%. DM pts had upregulation of the following pathways: TNF alpha signaling, inflammatory response, IL-6 JAK STAT3 signaling, heme metabolism, and the p53 pathway vs non-DM pts. Gene ontology analysis and individual differential gene expression profiles will be reported at the meeting. Conclusions: Our study found that pre-existing DM is associated with upregulation of inflammatory pathways in pts with PCa These hypothesis-generating results need external validation. Identification of transcriptomic biomarkers in these subsets of pts may help with further drug development. [Table: see text]
Survival outcomes in metastatic castration-resistant prostate cancer in the up-front treatment era.
Authors: Shunsuke Kamijo, Yushi Naito, Masashi Kato, Akiyuki Yamamoto, Toyonori Tsuzuki
Journal: Journal of Clinical Oncology (2023)

336 Background: Several studies have shown that the survival outcome of patients with metastatic prostate cancer after progression to metastatic castration-resistant prostate cancer (mCRPC) appears to be independent of a variety of prognostic factors, suggesting that prolonged time-to-CRPC is important for overall survival. However, the findings of these studies are based on data before the clinical application of up-front therapies such as docetaxel, abiraterone, enzalutamide, and apalutamide for hormone-sensitive metastatic prostate cancer (mHSPC), and the survival of patients with mCRPC with disease progression on up-front treatment has not been fully investigated. Methods: We retrospectively identified 318 patients diagnosed with treatment-naïve mHSPC between March 2014 and January 2022 from our database of 13 affiliated institutions. The patients included in this study were those who received the first-line treatment for mHSPC and progressed to mCRPC and received a second-line treatment. We defined the up-front group as patients who received abiraterone, apalutamide, or enzalutamide in addition to androgen deprivation therapy (ADT) as the first-line treatment for mHSPC, and the vintage group as patients who received ADT alone or bicalutamide or flutamide in addition to ADT. We compared the time-to-CRPC in each group, i.e., the time from diagnosis of mHSPC to progression to mCRPC. We also compared the overall survival (OS) after CRPC and the progression-free survival (PFS) after CRPC, calculated from the diagnosis of castration resistance, between the up-front group and the vintage group. To minimize selection bias, we performed propensity score matching between the up-front group and vintage group and adjusted for covariates such as age, metastatic burden, and Gleason score. Results: Of the 318 patients, 100 were in the up-front group and 218 in the vintage group. Fifteen of the up-front group and 205 of the vintage group progressed to mCRPC within the observation period and received second-line treatment. Fourteen patients from each group were extracted for the analysis of survival after CRPC by propensity score matching, and the clinicopathologic variables in each group were well balanced. In the analysis of the propensity score-matched cohort, time-to-CRPC was significantly prolonged in the up-front group compared to the vintage group (median, not-reached vs. 10.7 months; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.12-0.28; p&lt;0.001), while OS after CRPC (median, 18.2 months vs. not-reached; HR, 13.80; 95% CI, 1.52-125.10; p=0.019) and PFS after CRPC (median, 4.7 months vs. not-reached; HR, 7.73; 95% CI, 2.05-229.19; p=0.003) were significantly shortened in the up-front group. Conclusions: Although overall survival of mHSPC has improved in the up-front therapy era compared to the vintage hormonal therapy era, survival after disease progression to mCRPC may be shortened.